基于EphA2/ephrinA1通路调控血管纤维增生重构探讨软脉煎防治动脉粥样硬化的作用机制

在动脉粥样硬化（atherosclerosis，AS）进展期，坏死核形成、斑块破裂常易引发急性心脑血管事件的发生。申请人前期研究发现，以补肾填精、化痰祛浊为治法的中药复方软脉煎联合常规西药治疗颈动脉粥样硬化，能够改善患者证候、缩小斑块面积、降低临床终点事件。近年来有研究表明，抑制血管纤维增生重构及炎症反应可以限制AS进展，而EphA2/ephrinA1信号通路及相关分子表达在血管重构及炎症反应中发挥重要作用。本研究在前期研究基础上，拟通过体内外实验，建立ApoE-/-动脉粥样硬化小鼠及平滑肌细胞模型，采用分子生物学技术，沉默EphA2基因，观察AS发展过程中EphA2/ephrinA1及其相关信号通路的基因和蛋白的表达以及斑块成分、炎症因子等的变化，并明确软脉煎对AS的效应及EphA2/ephrinA1的影响，从调节血管重构及炎症反应角度明确软脉煎延缓动脉粥样硬化进展的分子机制。

The formation of necrotic cores and and disruption of vulnerable plaques in advanced lesion of atheroclerosis(AS) often cause the occurrence of acute cardiovascular events. The applicant's previous study found that Ruanmai decoction which can tonifying kidney and essence, resolving phlegm and removing turbidity combined with conventional western medicine could improve the syndrome, reduce the plaque area and reduce the clinical endpoint. In recent years, studies have shown that inhibition of fibroproliferative remodeling and inflammation is able to control the progress of atherosclerosis, EphA2/ephrinA1 and its related signaling pathway plays an important role in vascular remodeling and inflammation. This study is based on the previous research and designed to establish ApoE-/- mice and smooth muscle cells of AS model in vivo and in vitro, by the use of molecular biology techniques, knockdown EphA2 gene, to observe the EphA2/ephrinA1 and its related genes and proteins, inflammatory response factors, genes and proteins related with proliferation remodeling and phenotypic transformation of smooth muscle cell and the composition of plaque. And to clarity the effect of Ruanmai decoction on the atheroclerosis and EphA2/EphrinA1 signaling pathway, and the molecular mechanism of Ruanmai decoction in delaying the progression of atherosclerosis from the perspective of regulating vascular remodeling and inflammatory response.